Early conventional cardiac pacing techniques sought to calculate a target heart rate based on metabolic demand. These techniques included measuring a patient's respiration rate or “breathing rate” as a measure of metabolic demand and selecting a heart rate that corresponded in some way to this breathing rate. The breathing rate was thought to correspond to oxygen consumption (VO2), which in turn was known to be a fairly accurate indicator of metabolic demand, that is, absolute work intensity. Within a very narrow range, individuals exercising at the same intensity have the same VO2, or need for oxygen. Using an assumption that breathing rate is a good measure of VO2, conventional cardiac pacing devices were designed to increase the heart rate in response to an increased breathing rate.
A simple relationship of linear proportionality between heart rate and breathing rate adopted in conventional pacemakers is not very effective in several important circumstances. During sleep apnea (a common occurrence for many heart failure patients) and during exercise, more sophisticated techniques are needed to effectively establish a link between a given heart rate and a complementary breathing rate.
In general, while a person's breathing rate is roughly a derivative indicator of oxygen consumption, a much better indicator is minute ventilation (MV). A patient may increase oxygen intake not only by increasing the breathing rate, but even more so by changing tidal volume, i.e., the volume of air inspired with each breath. MV is a better measure of VO2 than the breathing rate alone because MV is the product of the breathing rate times the tidal volume of each breath, that is, the volume of air inspired over a period of time, usually one minute. At rest, an average adult MV is about 6 liters of air per minute (air is approximately 20% oxygen), corresponding to the oxidation of enough fuel to provide the work intensity expected in an average adult at rest.
The tidal volume component of MV is also dependent on two other “ventilations,” alveolar ventilation (VA) and dead space ventilation (VD). VA is the volume of air inspired per minute that reaches the alveoli and takes part in gas exchange (transfer of oxygen and carbon dioxide across the pulmonary capillaries). VD represents a volume of air that reaches the lungs but does not take part in gas exchange and is not considered part of VA.
During exercise, working muscles can increase their oxygen consumption immensely: for some muscles, up to one hundred times their resting rate of oxygen consumption. Averaged over the entire body, oxygen consumption can increase 20-25 times from the resting rate. The need for oxygen increases as the intensity of the exercise increases because aerobic pathways for producing energy must increasingly be used over anaerobic pathways.
As exercise increases, a person's breathing rate increases from approximately six to approximately twelve breaths per minute to a maximum of approximately sixty breaths per minute. Furthermore, the tidal volume can increase from approximately 0.5 liters per breath to approximately 2-3 liters per breath. These dramatic increases are responsible for a twenty to twenty-five-fold increase in MV in some adults during intense exercise, from six liters of air per minute at rest to 150 liters of air per minute. The increase in tidal volume is responsible for most of the dramatic increase in MV, not the increase in breathing rate.
The stimulus for increasing the MV during exercise is not well-understood. Carbon dioxide is the most well-known stimulator of the respiratory control centers of the central nervous system, but the level of carbon dioxide in the blood does not rise much during exercise, due to its rapid expiration in the lungs. The stimulus may proceed from proprioceptors of muscle activity or from an increase in blood potassium during muscular activity.
As the MV increases during exercise, the amount of blood perfused through the lungs increases proportionately. To pump the blood faster, the cardiac output (CO)—the heart rate multiplied by the stroke volume of the heart-increases during exercise. The heart rate may increase from approximately 60 beats per minute to approximately 200 beats per minute in a healthy young adult. Adult heart rates above 200 beats per minute do not increase CO further as the heart does not have time to fill properly. The stroke volume of the heart may increase from approximately 80 milliliters (mls) per beat to approximately 150 ml per beat in athletes. This allows the CO to vary from approximately 5 liters/minute at rest to approximately 30 liters per minute during intense exercise. It is difficult to appreciably increase the heart rate and stroke volume beyond the values above. If the myocardium is stretched beyond the maximum stroke volume, the heart and its pumping action get weaker, not stronger. Hence, the cardiovascular system and not the respiratory system may be the limiting factor in how intensely a patient can exercise.
The MV (which is a measure of ventilation) and the CO (which is a measure of blood perfusion) can have the same units—liters per minute. As exercise commences, the ideal 1:1 ratio between ventilation and perfusion remains linear. As exercise progresses, MV increases rapidly-both the breathing rate and the tidal volume increase together. The consumption of oxygen (VO2) and the MV remain linearly related, until humans reach between 55-75% of their maximum ability to work and to consume oxygen (VO2 max). Beyond this 55-75% level of VO2 max—a level known as the “ventilatory breakpoint”—the MV rises exponentially. The departure of MV from a linear relationship with VO2 after the breakpoint is thought to occur to increase evaporative heat loss from the lungs during intense exercise, and to increase the expiration of carbon dioxide, which lowers the concentration of H+ ions generated by increasing levels of lactic acid from the muscles. Thus, during exercise, there are many factors that could affect the relationships between heart rate, breathing rate, and tidal volume in a cardiac patient. The same is true during sleep apnea.
Sleep apnea is a serious malady, especially for those afflicted with heart failure. Symptoms of sleep apnea include not only the well-known cessation of breathing but also snoring, breath holding, rapid awakening, headaches, and more chronically, depression, irritability, fatigue, and memory loss.
Apnea is deemed to be present when dyspnea, that is, breathing difficulty, causes blood oxygenation and tissue oxygen saturation to decrease, sometimes to harmful levels. When apnea occurs, control centers in the brain react with a mild shock reaction, which can include release of norepinephrine, thereby arousing the apneic patient. Regular breathing ensues for a while with normal exchange of oxygen and accumulated carbon dioxide. Severe sleep apnea, however, may result in hundreds of episodes of oxygen desaturation during a night's sleep. Many apneics are not aware of the nightly malady, and are baffled during the daytime as they experience the long term effects of their condition. Sleep apnea can be classified as “obstructive” if the sleep apnea results from mechanical airway blockage, for example, due to partial collapse of the trachea during sleep or as “central” if the condition results from neurological dysfunction higher up in the central nervous system. “Mixed” sleep apnea includes a combination of mechanical and neurological causes. Sleep apnea can be life-threatening when it occurs in conjunction with coronary artery disease (CAD) or congestive heart failure (CHF or “heart failure”). Not only does sleep apnea place a tremendous burden on the heart and the entire cardiopulmonary system directly, but also circumvents normal sleep architecture, which affects the heart indirectly when ineffective sleep is chronic. Apneics, because of low blood oxygenation, are at an increased risk for hypertension, arrhythmias, heart attack, and stroke.
Approximately fifty percent of patients with heart failure suffer from sleep apnea, including approximately ten percent who suffer from obstructive type sleep apnea and approximately forty percent who suffer from central type sleep apnea. Sleep apnea and certain types of CHF exacerbate each other because of a negative synergy between the gas exchange problem during apnea and the oxygen distribution problem characteristic of CHF.
CHF is a condition in which a weakened heart cannot pump enough blood to body organs. Heart failure may affect either the right side, left side, or both sides of the heart. The weak pumping action causes fluid to back up into other areas of the body including the liver, gastrointestinal tract, and extremities (right-sided heart failure), or the lungs (left-sided heart failure). Heart failure patients have characteristic pulmonary edema or pitting edema of the lower legs.
For many heart patients who lack effective respiration, the above-described states of sleep apnea and physical exercise present challenges and opportunities in breathing rate regulation. Because the heart and lungs are intimately related members of the cardio-pulmonary system, a normal heart rate for a given physical state should provide a good basis for regulating a corresponding breathing rate, but more sophisticated techniques are needed to effectively link a given effective heart rate with a complementary effective breathing rate during times of stress, such as sleep apnea or exercise.